The goal of this project is to develop a smart neural prosthesis capable of producing an adjustable stimulation pattern for producing over-ground walking. The prosthesis will utilize intraspinal microstimulation (ISMS) to activate the motor neuron pools in the ventral horn of the lumbosacral region of the spinal cord where functional movements of the lower extremities can be restored. Extensive research has been conducted to validate the existence of a central pattern generator (CPG) which controls locomotion. This neural network is thought to integrate a preconditioned timing pattern as well as afferent feedback through the dorsal root from the lower extremities to produce coordinated and stable movements during locomotion. ISMS is a novel method of neural stimulation using ultra fine wires in the spinal cord to deliver electrical stimuli in activating the neuron pools in the ventra horn of the spinal cord. It has been demonstrated in cats that ISMS possesses the ability to generate sufficient force to support the weight of the hind limbs in addition to the desired leg movements required for locomotion. The aims of the present project are to develop a mobile, neural prosthesis capable of producing an adjustable stimulation pattern across different ISMS electrodes where the amplitude adjusts based on intrinsic and sensory conditions. The prosthesis will integrate afferent feedback in the form of external sensor signals or neural recordings from the dorsal root ganglia (DRG) as well as predetermined intrinsic timing thresholds to produce a changing stimulation waveform similar to what is observed in the biological CPG. Previous work using ISMS has mapped which movements are activated at different locations along the spinal cord and this information will be used to produce efficient functional movements and load bearing forces necessary for over-ground walking. By effectively programming the prosthesis, it will produce stimulation patterns which can adapt to perturbations such as slipping, tripping, and muscle fatigue by utilizing the afferent feedback. The success and reliability of the neural prosthesis in a cat model will lead towards the first device of its kind which can be used in a clinical setting involving humans with spinal cord injury PUBLIC HEALTH RELEVANCE: The proposed project is relevant to public health because it will provide progress towards the development of a neural prosthesis for individuals with spinal cord injury (SCI). While current studies are being conducted in cats, its success will lead towards the implementation of a neuroprosthesis for future use in a clinical setting.